Mucopolysaccharidosis

The diagnosis of MPS is based on a combination of clinical symptoms, increased urinary GAG levels, enzyme activity testing, and genetic analysis. Early diagnosis is critical to maximizing the effectiveness of treatment.

Diagnostic Steps

• Urine test: Qualitative and quantitative analysis of GAGs (e.g., heparan sulfate, dermatan sulfate)
• Blood or leukocyte test: Measurement of specific enzyme activity (for screening and confirmation)
• Genetic testing: Identification of mutations in the causative gene (definitive diagnosis)
• Imaging studies: Evaluation of abnormalities in the spine and joints, skull thickness, and brain MRI (especially for MPS III)
• Multidisciplinary assessment: Including audiometry, echocardiography, and pulmonary function testing

Currently, MPS is not curable, but various treatment options are available to slow disease progression and improve quality of life.

Enzyme Replacement Therapy (ERT)

ERT involves intravenous infusion of the deficient enzyme to reduce GAG accumulation in tissues. Approved therapies exist for MPS I (laronidase), II (idursulfase), IVA (elosulfase alfa), and VI (galsulfase). The earlier the therapy is initiated, the more effective it tends to be. However, ERT does not cross the blood-brain barrier, which limits its effect on central nervous system symptoms.

Hematopoietic Stem Cell Transplantation (HSCT)

In MPS I (Hurler), early transplantation before the age of two can help preserve cognitive function and improve long-term survival and quality of life. However, there are risks of complications and challenges in finding suitable donors.

Supportive Care

Supportive treatment includes hearing aids, continuous positive airway pressure (CPAP) for sleep apnea, cardiac medications, and orthopedic surgery. A multidisciplinary and individualized approach is essential based on the patient's condition.

Novel treatments for overcoming limitations of current treatment

CNS-Penetrating ERT

Conventional ERT does not cross the blood-brain barrier (BBB) and therefore is ineffective for central nervous system (CNS) symptoms. To overcome this limitation, receptor-mediated transport technologies are being applied to enable enzymes to cross the BBB, or direct administration into the ventricles or subarachnoid space is being developed. Some clinical trials have reported promising outcomes.

Gene Therapy

This approach involves using viral vectors (primarily adeno-associated virus, AAV) to deliver the deficient gene into the patient’s body, allowing continuous production of the enzyme. A single administration may yield long-term therapeutic effects, and clinical trials are actively ongoing for MPS I, II, III, and others.